8-80693070-C-T

Variant names:

• chr8-80693070-C-T
• NM_001033723.3:c.259G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001033723.3(ZNF704):​c.259G>A​(p.Ala87Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF704 NM_001033723.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32

Genes affected

ZNF704 (HGNC:32291): (zinc finger protein 704) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF704	NM_001033723.3	c.259G>A	p.Ala87Thr	missense_variant	Exon 3 of 9	ENST00000327835.7	NP_001028895.1
ZNF704	NM_001367783.1	c.781G>A	p.Ala261Thr	missense_variant	Exon 3 of 9		NP_001354712.1
ZNF704	XM_017013725.2	c.283G>A	p.Ala95Thr	missense_variant	Exon 3 of 9		XP_016869214.1
ZNF704	XR_928797.3	n.1205G>A		non_coding_transcript_exon_variant	Exon 3 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF704	ENST00000327835.7	c.259G>A	p.Ala87Thr	missense_variant	Exon 3 of 9	1	NM_001033723.3	ENSP00000331462.3
ZNF704	ENST00000519936.2	c.781G>A	p.Ala261Thr	missense_variant	Exon 3 of 9	5		ENSP00000427715.2
ZNF704	ENST00000520336.1	n.270G>A		non_coding_transcript_exon_variant	Exon 3 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.259G>A (p.A87T) alteration is located in exon 3 (coding exon 2) of the ZNF704 gene. This alteration results from a G to A substitution at nucleotide position 259, causing the alanine (A) at amino acid position 87 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.81	D;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.97
MutPred		0.36		Gain of glycosylation at A87 (P = 0.0349);Gain of glycosylation at A87 (P = 0.0349);
MVP		0.64
MPC		1.3
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.79
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-81605305;